Work in the fourth year of this proposal will focus on "non acid-base" factors in brain extra-cellular and intra-cellular fluid which may effect pulmonary ventilation and on the regulatory mechanisms for brain intra- and extra-cellular <H ion>. Ventricular-cisternal perfusion techniques will be used in awake dogs and rats to study the role of these unknown factors. Analysis of intra-cellular pH and turnover of brain neurotransmitters in chronic hypoxia provide the focus of our work on possible tissue mechanisms. Regulation of brain ECF <HCO3> and <H ion> during hypocapnia will focus on the problem of duration of hypocapnia and the relative contribution of systemic and local mechanisms in brain to the regulation of CSF <HCO3>. Investigations of the problems have important implications to the regulation of ventilation in healthy persons and chronic disease states. BIBLIOGRAPHIC REFERENCES: Glehill, N., G.J. Beirne and J.A. Dempsey. "Renal response to short-term hypocapnia in man." Kidney International, Vol. 8, 376-386, 1975. Pellegrino, D.A. and J.A. Dempsey. "Dependence of CSF on plasma bicarbonate during hypocapnia and hypoxemic hypocapnia." Resp. Physiol., 26:11-16, 1976.